signal transduction (cell communication 1)

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powerpoint presentation signal transduction (cell communication 1) dr. fiona murray school of medical sciences fmurray@abdn.ac.uk reading rang, dale and ritter. rang and dale’s pharmacology 8th edition: ch3 objectives introduce the 4 main types of receptors in signal transduction objectives – lecture 1 overview of signal transduction types of receptors ligand-gated ion channels g protein–coupled receptor g proteins effectors of g proteins second messengers (camp, ip3, dag, rhoa) tyrosine kinase linked receptors nuclear/intracellular receptors general summary objectives – lecture 1 overview of signal transduction types of receptors ligand-gated ion channels g protein–coupled receptor g proteins effectors of g proteins second messengers (camp, ip3, dag) tyrosine kinase linked receptors nuclear/intracellular receptors general summary information is transmitted from outside the cell to inside the cell. signal is transduced, amplified and translated into a response. signal transduction 1 3 2 infinite variety of biological signals: hormones, neurotransmitters, cytokines, growth factors, chemoattractants, and light 6 …

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n shift to the right of the log agonist concentration – effect curve but no change in the max response) most common pharmacological antagonists are competitive antagonists 10 basic concept: non-competitive antagonists ligand/agonist + effector cellular response cell membrane x x x non-competitive antagonist: usually bind at a site distinct from the agonist to prevent activation of the receptor no amount of agonist can overcome the antagonism 11 types of receptor there are four main types of receptors in signal transduction: ligand-gated ion channels (ionotropic) g protein-coupled receptors (gpcr, metapotropic) tyrosine kinase linked receptors nuclear/intracellular receptors additional families of receptors include tgfβ, tnfα, cytokine, wnt, hedgehog and notch * types of receptor 13 critical features of signal transduction sensitivity high affinity (attraction) between ligand and receptor co-operativity small change in [ligand] produces a large change in response amplification via enzyme cascades e.g. g proteins interaction between ligand and receptor is …

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why are ion channels important? these receptors control the fastest synaptic event in the nervous system (millisecond) facilitate transport of ions in/out of the cell (high to low concentration) changes membrane potential (vm, normally -70mv) if vm becomes more negative the cell are more difficult to stimulate if vm becomes less negative the cell is easier to stimulate (depolarization) ……..action potential……muscle contraction ligand gated-ion channels β, γ and δ subunits regulate desensitization 21 g protein-coupled receptors (gpcrs) g r e r - receptor g - g protein e - effector ligand cellular effect g protein-coupled receptors membrane bound receptor linked through g protein to enzyme or ion channel intermediate required, fast (seconds) 23 gpcr agonists and antagonists play key roles in therapy of multiple widespread diseases: examples cardiovascular - coronary artery disease, congestive heart failure, hypertension pulmonary - asthma, chronic obstructive pulmonary disease (copd), hypertension neurological - migraine, parkinson’s disease, …

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, prostaglandins, thromboxane a2) ip, ep1-4, dp1-2, fp, tp adenosine adenosine (a1, a2a, a2b, a3) * some neurotransmitters act on both gpcrs and ligand-gated ion channels important bit! deletion does not affect ligand binding but does impede signal transduction g protein-coupled receptors (gpcrs) 27 g protein binding domain is responsible for down stream effects. adrenaline binds to and activates r downstream effects are cholinergic in character ach adrenaline g protein-coupled receptors (gpcrs) – what determines downstream effects? 28 g protein receptor – intermediary - effector (g protein) middle management, comprised of α, β, γ subunits α subunit can breakaway from βγ subunits (both signal) bind guanine nucleotides highly mobile within membrane promiscuous – can interacts with a number of effectors gtpase activity (switch off) 29 gpcrs act as gefs guanine nucleotide exchange factors (gefs) pi gef gtpase a gefs or a gtpase are not a kinases 31 g-protein cycle g …

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is thought to be a problem associated with long acting -agonists * homologous, desensitization - g protein-coupled receptor kinases (grk) phosphorylate the gpcrs, uncoupling gα, and facilitating β-arrestin. β-arrestin initiates endocytosis of receptor intracellular vesicles - dephosphorylation recycling of receptor back to plasma membrane 37 g protein-independent signaling β-arrestins uncouple gpcrs from g proteins and promotes endocytosis β-arrestins also function as gpcr signal transducers by forming complexes with signaling proteins such as src, erk and akt 38 what next? ligand bound gpcr activation of g protein activation of enzyme second messenger image1.png image2.png image3.png image4.emf image5.png image6.png image7.png image8.jpeg image9.png image10.emf image11.jpeg image12.jpeg image13.jpeg image14.jpeg image15.png image16.jpeg image17.jpeg activation of adenylyl cyclase ceases. similar amplification probably occurs in signaling from receptors coupled to other g proteins and some other types of receptors whose activa- tion induces synthesis of second messengers. a second level of amplification is illustrated by the camp-mediated …

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powerpoint presentation signal transduction (cell communication 1) dr. fiona murray school of medical sciences fmurray@abdn.ac.uk reading rang, dale and ritter. rang and dale’s pharmacology 8th edition: ch3 objectives introduce the 4 main types of receptors in signal transduction objectives – lecture 1 overview of signal transduction types of receptors ligand-gated ion channels g protein–coupled receptor g proteins effectors of g proteins second messengers (camp, ip3, dag, rhoa) tyrosine kinase linked receptors nuclear/intracellular receptors general summary objectives – lecture 1 overview of signal transduction types of receptors ligand-gated ion channels g protein–coupled receptor g proteins effectors of g proteins second messengers (camp, ip3, dag) tyrosine kinase linked receptors nucle...

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